Evidence map›Paper›PMID 24707053›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Mapping protein conformational heterogeneity under pressure with site-directed spin labeling and double electron-electron resonance.

Michael T Lerch, Zhongyu Yang, Evan K Brooks, Wayne L Hubbell

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed.

  1. Elliptical β-barrel deformation underlies gating in VDAC1.Protein science : a publication of the Protein Society · 2026
    Article
  2. Hydraulic Activation of the AsLOV2 Photoreceptor.bioRxiv : the preprint server for biology · 2025
    Article
  3. Review
  4. Protein Modeling with DEER Spectroscopy.Annual review of biophysics · 2025
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Viewing rare conformations of the βProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  10. GProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  11. High-pressure EPR spectroscopy studies of theApplied magnetic resonance · 2017
    Article
  12. Article
  13. Coherent pump pulses in Double Electron Electron Resonance spectroscopy.Physical chemistry chemical physics : PCCP · 2016
    Article
  14. Article
  15. Article
  16. Structure-relaxation mechanism for the response of T4 lysozyme cavity mutants to hydrostatic pressure.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Michael T LerchJules Stein Eye Institute and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095.
Zhongyu Yang
Evan K Brooks
Wayne L Hubbell

Funding

Vision Research Core at UCLAP30EY000331 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Xian-Jie Yang · 1985 to 2026
$16.8M
TR&D Project 3P41EB001980 · NIBIB · MEDICAL COLLEGE OF WISCONSIN · PI KLUG, CANDICE S · 2003 to 2017
$16.3M
MOLECULAR BASIS OF MEMBRANE EXCITATIONR01EY005216 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HUBBELL, WAYNE L · 1985 to 2019
$9.8M
CHEMISTRY BIOLOGY INTERFACE TRAINING PROGRAMT32GM008496 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYNARD, HEATHER D · 1993 to 2019
$6.3M
NEI NIH HHS 2P30 EY00331NEI NIH HHS 2R01 EY05216NEI NIH HHS P30 EY000331NEI NIH HHS R01 EY005216NIBIB NIH HHS P41 EB001980NIGMS NIH HHS T32 GM 008496NIGMS NIH HHS T32 GM008496
6 · The paper itself

Abstract

The dominance of a single native state for most proteins under ambient conditions belies the functional importance of higher-energy conformational states (excited states), which often are too sparsely populated to allow spectroscopic investigation. Application of high hydrostatic pressure increases the population of excited states for study, but structural characterization is not trivial because of the multiplicity of states in the ensemble and rapid (microsecond to millisecond) exchange between them. Site-directed spin labeling in combination with double electron-electron resonance (DEER) provides long-range (20-80 Å) distance distributions with angstrom-level resolution and thus is ideally suited to resolve conformational heterogeneity in an excited state populated under high pressure. DEER currently is performed at cryogenic temperatures. Therefore, a method was developed for rapidly freezing spin-labeled proteins under pressure to kinetically trap the high-pressure conformational ensemble for subsequent DEER data collection at atmospheric pressure. The methodology was evaluated using seven doubly-labeled mutants of myoglobin designed to monitor selected interhelical distances. For holomyoglobin, the distance distributions are narrow and relatively insensitive to pressure. In apomyoglobin, on the other hand, the distributions reveal a striking conformational heterogeneity involving specific helices in the pressure range of 0-3 kbar, where a molten globule state is formed. The data directly reveal the amplitude of helical fluctuations, information unique to the DEER method that complements previous rate determinations. Comparison of the distance distributions for pressure- and pH-populated molten globules shows them to be remarkably similar despite a lower helical content in the latter.

Indexed as

ElectronsHydrostatic PressureSpin LabelsAnimalsApoproteinsElectron Spin Resonance SpectroscopyFreezingHydrogen-Ion ConcentrationModels, MolecularMyoglobinProtein Structure, SecondarySperm WhaleapomyoglobinApoproteinsMyoglobinSpin Labelscompressibilitydipolar spectroscopyEPR

Identifiers

PMID24707053
PMCPMC3977274

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.